Aims: We analysed possible influence of perforin-dependent infiltration upon long-term mortality in patients with inflammatory cardiomyopathy (CMi). We previously demonstrated that left ventricular function deteriorates and progresses to substantial cardiac dysfunction in patients with perforin-positive cardiac cell infiltration.
Methods and Results: Between 2003 and 2013, 2389 consecutive patients with clinically suspected CMi who underwent endomyocardial biopsy (EMB) were enrolled. EMBs were performed at first admission after exclusion of ischemic or valvular heart disease, and CMi was confirmed in 1717 patients. Follow-up was up to 10.1 years (median 0.47y; IQR 0.03y - 2.56y) and information on vital status was obtained from official resident data files. Multivariable statistical analysis was conducted for all CMi patients regarding significant predictors of all-cause mortality or need for heart transplantation (HTX). Multiple Cox regression analysis revealed perforin above the calculated cut off point of 2.9/mm2 as a strong predictor of impaired survival with hazard ratio (HR) of 1.881, 95% confidence interval (CI) 1.177-3.008, p=0.008, independent of LV function and other myocardial inflammation markers (CD3, Mac-1, LFA-1, HLA-1, and ICAM-1). Unexpectedly, male sex emerged as another strong adverse predictor of survival in CMi (HR 1.863, CI 1.096-3.168, p=0.022). Whereas LVEF course is adversely affected by myocardial perforin, multivariate analysis indicates that LVEF explains only part of the observed overall mortality.
Conclusion: High perforin-positive cardiac cell infiltration and male gender are independend adverse predictors of long term-mortality in CMi. Furthermore, exact quantification of immunohistochemically detected infiltrates is necessary to assess the prognosis.